Preliminary experiments demonstrate that prenatal exposure to cocaine both prior to and during gestation results in significant suppression of in vitro and in vivo measures of cellular immunity. The overall goal of the proposed studies is to further examine these effects and determine whether prenatal cocaine exposure increases the susceptibility of offspring to other drugs and stressors. To meet this goal the following specific aims will be carried out: Specific Aim #1: To determine the effects of prenatal cocaine exposure on in vitro and in vivo immune parameters in offspring under controlled conditions. These studies will examine in vitro (lymphocyte phenotype expression, mitogen-induced proliferation and natural killer (NK) cell activity) and in vivo (antigen-elicited humoral and cellular immune responses) at 50 days postnatal in offspring born of dams exposed to cocaine prior to and during gestation. Such effects will be compared to pups born of pairfed and vehicle- treated dams to control for the effects (if any) of nutrition and handling on similar immunological indices. The contribution of changes in maternal behaviors of cocaine-treated dams to subsequent immune reactivity in pups will also be examined by comparing immune reactivity of fostered and nonfostered pups. Both male and female offspring will be examined to determine gender effects (if any) in immune reactivity. Finally, sampling from individual litters will be limited to control for specific litter effects that might confound interpretation of effects of prenatal exposure. Specific Aim #2: To characterize the temporal relationship of the effects of prenatal cocaine exposure on in vitro and in vivo immune parameters in offspring. Although prenatal cocaine exposure reduces immune responses 50 days postnatally, it is unknown when these effects first appear and how long they will persist. Therefore, following prenatal exposure to cocaine various immune indicators will be examined at postnatal days 10, 20, 50 and 100. Specific Aim #3: To determine the exposure period sufficient for the production of in vitro and in vivo immune changes in prenatally exposed offspring. Although prenatal cocaine exposure both prior to and during gestation decreases cellular immunity, it is unknown whether the immunosupression in the offspring is a function of exposure period. Therefore, measures of immunity will be measured 50 days postnatally in offspring born of dams exposed to cocaine prior to, during and both prior to and during gestation. Specific Aim #4: To examine in vitro immune sensitivity of offspring prenatally exposed to cocaine to subsequent drug and stress challenges. A number of recreational drugs, including cocaine, affect immune responsitivity in adult animals with no history of prenatal cocaine exposure. In these studies, the effects of prenatal cocaine exposure on immune functioning and how such exposure may alter the vulnerability of the immune system to subsequent challenges such as cocaine, nicotine, morphine, restraining stress or endotoxin (LPS) will be determined.